I mean, of all time. I'm going with killing Valeria (Speaking of, how did he lose her/the armor?) and or sending Franklin to literal Hell. He also kidnapped Franklin and offered his soul for his mother's, that was pretty bad too, although that MIGHT have been a Doombot (It did happen before Siminson's run.). Didn't he also brainwash Kristoff at one point? Doom hasn't done too many truly horrific things (At least compared to the Joker or Norman Osborn.), but those were pretty dang bad.

In addition to all of the other items listed in this thread, he's also:

Cloned himself, called his clone his "son", then killed his son when the clone realized what a monster dear old dad was.

Killed Cassie Lang. Bringing her back to life doesn't get him off the hook.

May have caused Avengers Disassembled by manipulating Wanda.

Experimented with drugs on Yancy Street kids for some reason

When ruling Battleworld tossed anyone who disagreed with him over wall to be devoured by zombies and ultrons.

Wrote a fake diary allegedly written by Reed that made the other team members distrust Reed.

Dissected live Asgardians for fun

When Loki was a woman Doom fantasized about her being part of his harem. Not necessarily an evil thing, but interesting.